小RNA
Wnt信号通路
癌症研究
生物
结直肠癌
下调和上调
细胞周期蛋白D1
葛兰素史克-3
脱氮酶
N6-甲基腺苷
癌症
信号转导
细胞生物学
细胞周期
泛素
基因
甲基转移酶
遗传学
甲基化
作者
Hongyan Li,Ning Zhang,Xiuling Jiao,Cong Wang,Wenhao Sun,Yanyu He,Ganglin Ren,Shirui Huang,Mengjie Li,Ye Chang,Zihui Jin,Qipeng Xie,Xiaodong Zhang,Haishan Huang,Honglei Jin
摘要
MicroRNAs (miRNAs), the key regulator of gene expression, and N6-methyladenosine (m6A) RNA modification play a significant role in tumour progression. However, regulation of m6A-modified mRNAs by miRNAs in colorectal cancer (CRC), and its effect on progression of CRC, remains to be investigated.Expression of miR-6125 and YTH Domain-Containing Family Protein 2 (YTHDF2) was detected by western blotting and immunohistochemistry. The effects of miR-6125 and YTHDF2 on proliferative capacity of CRC cells were analysed using soft agar, ATP, CCK8 and EdU assays, and in animal experiments.MiR-6125 expression was downregulated markedly in CRC, and expression correlated negatively with tumour size and prognosis. MiR-6125 targeted the 3'-UTR of YTHDF2 and downregulated the YTHDF2 protein, thereby increasing the stability of m6A-modified glycogen synthase kinase 3 beta (GSK3β) mRNA. Increased GSK3β protein levels inhibited the expression of Wnt/β-catenin/Cyclin D1 pathway-related proteins, leading to G0-G1 phase arrest and ultimately inhibiting the proliferation of CRC cells.MiR-6125 regulates YTHDF2 and thus plays a critical role in regulating the Wnt/β-catenin pathway, thereby affecting the growth of CRC. Collectively, these results suggest that miR-6125 and YTHDF2 are potential targets for treatment of CRC.
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